rs2957692

Positions:

• chr11-10346572-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000532250.5(AMPD3):​c.-6+15863A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 151,982 control chromosomes in the GnomAD database, including 11,302 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.38 (11302 hom., cov: 32)
• Consequence: AMPD3 ENST00000532250.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.566

Genes affected

AMPD3 (HGNC:):

AMPD3 (HGNC:470): (adenosine monophosphate deaminase 3) This gene encodes a member of the AMP deaminase gene family. The encoded protein is a highly regulated enzyme that catalyzes the hydrolytic deamination of adenosine monophosphate to inosine monophosphate, a branch point in the adenylate catabolic pathway. This gene encodes the erythrocyte (E) isoforms, whereas other family members encode isoforms that predominate in muscle (M) and liver (L) cells. Mutations in this gene lead to the clinically asymptomatic, autosomal recessive condition erythrocyte AMP deaminase deficiency. Alternatively spliced transcript variants encoding different isoforms of this gene have been described. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAND1.11	NR_103765.1	n.501+15863A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AMPD3	ENST00000295663.9	n.50+15863A>G		intron_variant		1
AMPD3	ENST00000527261.5	n.501+15863A>G		intron_variant		1
AMPD3	ENST00000532250.5	c.-6+15863A>G		intron_variant		4		ENSP00000432707.1

Frequencies

GnomAD3 genomes AF: 0.376 AC: 57100 AN: 151864 Hom.: 11275 Cov.: 32

Gnomad AFR AF: 0.390

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.327

Gnomad ASJ AF: 0.365

Gnomad EAS AF: 0.0349

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.451

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.403

Gnomad OTH AF: 0.346

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.376 AC: 57195 AN: 151982 Hom.: 11302 Cov.: 32 AF XY: 0.376 AC XY: 27897 AN XY: 74264

Gnomad4 AFR AF: 0.391

Gnomad4 AMR AF: 0.328

Gnomad4 ASJ AF: 0.365

Gnomad4 EAS AF: 0.0349

Gnomad4 SAS AF: 0.282

Gnomad4 FIN AF: 0.451

Gnomad4 NFE AF: 0.403

Gnomad4 OTH AF: 0.349

Alfa AF: 0.378 Hom.: 1756

Bravo AF: 0.363

Asia WGS AF: 0.163 AC: 568 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	4.7
DANN	Benign	0.58

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2957692; hg19: chr11-10368119;